Retinal microvascular abnormalities and stroke: a systematic review

Background: Lacunar strokes account for 25% of ischaemic strokes, but their precise aetiology is unknown. Similarities between the retinal and cerebral small vessels mean that clarification of the exact relationship between retinal microvascular abnormalities and stroke, and particularly with stroke subtypes, may aid understanding of the aetiology of lacunar stroke and stroke risk. Methods: A systematic review of the literature was performed by searching Medline and Embase to October 2007 for studies in humans that investigated the association between retinal microvascular abnormalities and prevalent or incident stroke. Data and calculated summary risk ratios (sRR) were extracted for associations between retinal microvascular abnormalities and stroke, including stroke subtypes where possible, adjusted for key variables. 37 papers from 22 different studies were included with 62 975 subjects (mean age 62 years) among whom there were 2893 strokes. Stroke identification and diagnosis methods varied. Results: Retinopathy was associated with incident stroke (sRR 2.1, 95% CI 1.7 to 2.6) and prevalent stroke (sRR 2.5, 95% CI 1.4 to 4.3). Incident stroke was also associated with retinal artery embolism (sRR 2.9, 95% CI 1.6 to 5.1) and venular widening (sRR 1.4, 95% CI 1.1 to 1.7). There was significant heterogeneity between studies for some associations. There were no data on retinal microvascular abnormalities and haemorrhagic versus ischaemic stroke or ischaemic stroke subtypes. Conclusions: Retinal microvascular abnormalities are associated with stroke, but more data are required to clarify associations between specific types of retinal microvascular abnormality and stroke, as well as between different stroke subtypes. Future retinal-stroke studies should concentrate on carefully diagnosing and accurately sub-typing ischaemic strok

Supplementary Material for: Plasma Biomarkers of Inflammation, Endothelial Function and Hemostasis in Cerebral Small Vessel Disease

<b><i>Background:</i></b> The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It is unknown if plasma biomarkers add predictive capacity beyond age and vascular risk factors in explaining WMH. <b><i>Methods:</i></b> We prospectively recruited patients presenting with non-disabling ischemic stroke, classifying them clinically and with the help of MRI as lacunar or cortical. We measured biomarkers of inflammation, endothelial dysfunction and hemostasis for >1 month after stroke and compared biomarker levels between stroke subtypes. We quantitatively calculated WMH. We used multiple linear regression analysis to model WMH as a function of age, sex, hypertension and smoking (the baseline model). We fitted exploratory models using plasma biomarkers as predictor variables to assess model improvement over baseline. <b><i>Results:</i></b> We recruited 125 patients. The lacunar group (n = 65) had lower tissue plasminogen activator (t-PA) levels in unadjusted (7.39 vs. 8.59 ng/ml, p = 0.029) and adjusted (p = 0.035) analyses compared with the cortical group (n = 60). There were no significant differences in the other plasma biomarkers. The results for t-PA were consistent with an updated meta-analysis, although the effect remains non-significant (standardized mean difference -0.08 (95% CI -0.25 to 0.09)). The baseline regression model explained 29% of the variance in quantitative WMH (R² 0.289). Inflammatory biomarkers showed minor improvement over baseline (R² 0.291), but the other plasma biomarkers did not improve the baseline model. <b><i>Conclusion:</i></b> Plasma t-PA levels appear to differ between lacunar and cortical stroke subtypes, late after stroke, independent of age, sex and vascular risk factors and may reflect endothelial dysfunction. Except for a minor additional predictive effect of inflammatory markers, plasma biomarkers do not relate to WMH severity in this small stroke population

Vascular dysfunction-The disregarded partner of Alzheimer's disease

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.Neuro Imaging Researc